Serena Williams feels the pain of defeat in Paris as she will not be defending her title. Photo: AFP

Defending champion and world number one Serena Williams was knocked out of the French Open on Wednesday throwing the women's tournament wide open.

The top seed lost 6-2, 6-2 in the second round to the world number 35 Garbine Muguruza, of Spain, with her defeat coming just an hour after sister Venus also went out 2-6, 6-3, 6-4 to Slovak teenager Anna Schmiedlova.

It was the earliest exit for a defending champion at Roland Garros since 2005 when Anastasia Myskina of Russia went out in the first round.

I just couldn't serve. But you can't be on form every day. I hate to be off at a grand slam

Serena Williams

But it was a different story in the men's, as Serbia's Novak Djokovic eased past Jeremy Chardy 6-1, 6-4, 6-2.

Swiss Roger Federer also reached the third round with a 6-3, 6-4, 6-4 win over Argentine qualifier Diego Schwartzman.

Wednesday's defeat was Serena's worst at a grand slam in terms of games won and was only the second time in her career she had been beaten at a major in the round of 64.

The last time that happened was on her debut at the 1998 Australian Open.

It was also just the fourth time the Williams sisters had lost on the same day at a major.

"Nothing worked today," said 17-time major winner Serena who hit just eight winners and a huge 29 unforced errors with five double faults.

"I just couldn't serve. But you can't be on form every day. I hate to be off at a grand slam, but it happens. It's not the end of the world.

"I will have to work five times as hard to make sure it doesn't happen again," added the 32-year-old American who suffered her only other grand slam first round loss in Paris in 2012.

Muguruza, 20, immediately won praise for her performance.

"Shocker at the French - Serena loses to Garbine Muguruza. Garbine is here to stay, that's for sure, quite a talent," tweeted Martina Navratilova.

The young Spaniard was overjoyed by her performance. "Today's a great day," she said.

Serena'a defeat was good news for Maria Sharapova who is now the overwhelming title favourite with second seed Li Na having been knocked out in the first round on Tuesday.

The Williams sisters had been scheduled to meet in the third round. Instead the tournament will see Muguruza against Schmiedlova, the 19-year-old Slovak who ended 32-year-old Venus' 17th French Open with a 2-6, 6-3, 6-4 win.

Schmiedlova was just a month old when the American made her professional debut back in 1994. "It's the biggest win of my career," said world number 56 Schmiedlova.

This article appeared in the South China Morning Post print edition as Shocking earliest slam exit for Serena in 16 years